The objective of the proposed research is to determine the role of cell surface molecules in the regulation of cardiac electrogenesis. To achieve this goal, we will employ multidisciplined analyses of electrophysiological, biochemical and transport properties of cultured aggregates of embryonic chick heart cells. Canine ventricular muscle and Purkinje fibers will also be used to assess the importance of such molecules in the adult heart and to test the suitability of the tissue culture preparation as a model for further investigation. Intracellular recording, voltage clamp, radioisotope, biochemical and electron microscopic techniques will be utilized to answer the following questions: (a) How do these charged moieties influence the conductance mechanisms which underlie automaticity, and can their binding or removal induce spontaneous activity or alter rhythmicity? (b) Can the effects of multivalent cations upon electrophysiological properties be accounted for by "screening" or binding to specific cell surface anions, and can the resultant alterations in surface potential influence the actions of charged drugs upon membrane receptors? (c) How do cell surface molecules influence transport of ions across the cell membrane?